tbuckley/cabot-search huggingface dataset:
EPCT-07. Updated report on the pilot study of using MRI-guided laser heat ablation to induce disruption of the peritumoral blood brain barrier to enhance deliver and efficacy of treatment of pediatric brain tumors
Authors: Margaret Shatara, Karen Gauvain, Evan Cantor, Ashley Meyer, Andrea Ogle, Michele McHugh, Mary Beck, Tammy Green, Allison King, Andrew Cluster, Nicole Brossier, Joshua S Shimony, Mohamed S Abdelbaki, David D Tran, Jian Campian, Eric C Leuthardt, Joshua Rubin, David Limbrick
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: MRI-guided laser interstitial thermal therapy (LITT) is a minimally invasive, cytoreductive surgery useful for managing unresectable brain tumors. LITT disrupts the blood brain barrier (BBB) and facilitates chemotherapy delivery. We report the toxicity and outcome for pediatric brain tumors treated on a pilot trial of LITT and chemotherapy. The primary objectives were to quantify peritumoral BBB disruption following LITT and evaluate toxicity and efficacy. METHODS: The trial had two arms, A: patients with newly diagnosed gliomas underwent LITT followed by standard of care management, and B: patients with relapsed malignant brain tumors received 6 weeks of weekly doxorubicin post-LITT followed by maintenance etoposide. RESULTS: Between 2015 – 2018, six patients were enrolled: five on arm A (four with low-grade gliomas, one with high-grade glioma), one on Arm B with progressive anaplastic astrocytoma. All patients tolerated the procedure well; four experienced a transient hemiparesis post-LITT. The Arm B patient progressed and died of disease 2 months and 22 months post-LITT, respectively. The HGG patient received standard therapy and remains without disease progression 44 months post-LITT. One patient with LGG required additional treatment for disease progression 14 months post-LITT. Two patients with LGGs did not require additional therapy, now 51 and 41 months post-LITT. One patient was alive 24 weeks post-LITT and subsequently lost to follow-up. Peritumoral BBB disruption was analyzed in two ways: serum abundance of brain-derived proteins and MRI Dynamic contrast enhancement (DCE). Neuron-specific enolase were measurable in the serum of all patients, using ELISA up to 84 days post-LITT. DCE 2 weeks post-LITT demonstrated increased enhancement and FLAIR signal, consistent with BBB disruption and vasogenic edema. This effect was evident up to 4 months post-procedure. CONCLUSION: LITT is safe in children with brain tumors and can be combined with chemotherapy. DCE and serum brain-derived proteins can measure BBB disruption.
MEDB-41. Identifying a subgroup of patients with early childhood sonic hedgehog-activated medulloblastoma with unfavorable prognosis after treatment with radiation-sparing regimens including intraventricular methotrexate
Authors: Svenja Tonn, Denise Obrecht, Martin Sill, Michael Spohn, Till Milde, Torsten Pietsch, Brigitte Bison, Björn-Ole Juhnke, Nina Struve, Carsten Friedrich, André O von Bueren, Nicolas U Gerber, Martin Benesch, Natalie Jäger, Marcel Kool, Andrey Korshunov, Ulrich Schüller, Stefan M Pfister, Stefan Rutkowski, Martin Mynarek
Journal: Neuro-Oncology (2022)

Abstract PURPOSE/METHODS: Clinical and molecular risk factors in 142 patients &amp;lt;5 years with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) were investigated. Patients were diagnosed between 1992 and 2020 and treated with radiation-sparing approaches, 131 with intraventricular methotrexate. 14 patients with metastatic disease received high-dose chemotherapy. DNA methylation profiles of 77 sonic hedgehog (SHH)-activated medulloblastoma were reclassified according to the Heidelberg Brain Tumor Classifier Version 12.3. RESULTS: While metastatic disease or incomplete resection did not impact progression-free survival (PFS) and overall survival (OS), patients with MBEN had superior outcomes to DMB (5-year PFS 93% vs 71%, p=0.004; 5-year OS 100% vs 90%, p=0.026). Older patients had less favorable PFS (5-year PFS [&amp;gt;3 years] 47% vs 85% [&amp;lt;1 year] vs 84% [1-3 years], p&amp;lt;0.001). No TP53 mutations were detected (n=47). DNA methylation classification identified three subgroups: SHH-1v12.3 (n=39), SHH-2v12.3 (n=19), and SHH-3v12.3 (n=19), with distinct cytogenetic profiles (chromosome 2 gains in SHH-1v12.3, very few alterations in SHH-2v12.3, and chromosome 9q losses in SHH-3v12.3), age profiles (median age [years] SHH-1v12.3: 1.7, SHH-2v12.3: 0.9, SHH-3v12.3: 3.0, p&amp;lt;0.001), and histological distribution (SHH-2v12.3: 74% MBEN, SHH-1v12.3/SHH-3v12.3: 77%/79% DMB, p&amp;lt;0.001). PFS was more unfavorable in patients with SHH-3v12.3-medulloblastoma (5-year PFS 53% vs 86% [SHH-1v12.3] vs 95% [SHH-2v12.3], p=0.002), which remained the only risk factor on multivariable Cox regression for PFS. OS was comparable (5-year OS 94% [SHH-3v12.3] vs 97% [SHH-1v12.3] vs 100% [SHH-2v12.3], p=0.6). 8/9 patients with SHH-3v12.3-medulloblastoma received radiotherapy at relapse (6 craniospinal, 2 local [1 Gorlin syndrome, 1 BRCA2 germline mutation], 1 no radiotherapy [Gorlin syndrome]). CONCLUSION: We identify patients with an increased risk of relapse when treated with radiation-sparing approaches among children with early childhood SHH-medulloblastoma. If these tumors differ from SHH-3-medulloblastoma typically described in older children remains to be verified. Treatment recommendations need to consider cancer predisposition syndromes.
Per anal endoscopic myectomy for rectal neuroendocrine tumor invading submucosal deep layer and ending at the muscle layer
Authors: Yoshiyasu Kitagawa, Asuka Ishigaki, Osamu Sugita, Takuto Suzuki
Journal: Endoscopy (2022)

Endoscopic submucosal dissection (ESD) is an effective technique for treating rectal neuroendocrine tumors. However, it is technically challenging to ensure a proper resection margin if the tumor invades deeply into the submucosa and ends adjacent to the muscle layer. Recently, ESD with myectomy, called per anal endoscopic myectomy, has been developed for rectal lesions with severe fibrosis [1]. In the present study, we describe a successful case of per anal endoscopic myectomy for rectal neuroendocrine tumors.
Salvage high-intensity focused ultrasound for residual or recurrent cervical cancer after definitive chemoradiotherapy.
Authors: Fei Tang, Qin Zhong, Tingting Ni, Yanping Chen, Yuncong Liu, Jing Wu, Zhiyu Feng, Xiaokai Lu, Shisheng Tan, Yu Zhang
Journal: Journal of Clinical Oncology (2022)

e17524 Background: Approximately 30%-65% of patients have residual disease or subsequent recurrence after completion of chemoradiotherapy (CRT) treatment. The treatment of residual/recurrent cervical cancer in previously irradiated field is challenging and generally associated with a poor prognosis. Local treatments such as salvage surgery and re-irradiation are usually traumatic and have limited efficacy. High intensity focused ultrasound (HIFU) treatment can directly ablate solid tumors without damaging neighboring healthy tissue. However, the HIFU studies for these patients are limited. Over 10 years of experience gained with the management of HIFU in cervical cancer patients with residual disease or recurrence after CRT is reported here. Methods: 153 patients with residual or recurrent cervical cancer in previously irradiated field who received HIFU treatment between 2010 and 2021 were retrospectively analyzed. Adverse effects, survival benefit, and factors affecting prognosis were given particular attention. Results: A total of 36 patients (23.5%) achieved a partial response following HIFU treatment and 107 patients (69.9%) had stable disease. The objective response and disease control rates were 23.5% and 93.5%, respectively. The median progression-free survival (mPFS) and median overall survival (mOS) were 17.0 months and 24.5 months, respectively. Moreover, patients with lesions ≥ 1.40 cm before HIFU treatment and a shrinkage rate ≥ 30% after treatment had a higher mPFS and mOS, and patients with lesions ≤ 1.00 cm after HIFU treatment had a higher mPFS (P &lt; 0.05). All of the treatment-related adverse events were limited to minor complications, which included skin burns, abdominal pain and vaginal discharge. Conclusions: Many cervical cancer patients have few efficacious treatment options following chemoradiotherapy. This study demonstrates that HIFU treatment is likely a preferred option that can safely improve the local control rate and extend survival.
Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist <i>Salmonella</i> infection in mice
Authors: Yong Ge, Mojgan Zadeh, Mansour Mohamadzadeh
Journal: The Journal of Experimental Medicine (2022)

Deprivation of vitamin B12 (VB12) is linked to various diseases, but the underlying mechanisms in disease progression are poorly understood. Using multiomic approaches, we elucidated the responses of ileal epithelial cells (iECs) and gut microbiome to VB12 dietary restriction. Here, VB12 deficiency impaired the transcriptional and metabolic programming of iECs and reduced epithelial mitochondrial respiration and carnitine shuttling during intestinal Salmonella Typhimurium (STm) infection. Fecal microbial and untargeted metabolomic profiling identified marked changes related to VB12 deficiency, including reductions of metabolites potentially activating mitochondrial β-oxidation in iECs and short-chain fatty acids (SCFAs). Depletion of SCFA-producing microbes by streptomycin treatment decreased the VB12-dependent STm protection. Moreover, compromised mitochondrial function of iECs correlated with declined cell capability to utilize oxygen, leading to uncontrolled oxygen-dependent STm expansion in VB12-deficient mice. Our findings uncovered previously unrecognized mechanisms through which VB12 coordinates ileal epithelial mitochondrial homeostasis and gut microbiota to regulate epithelial oxygenation, resulting in the control of aerobic STm infection.
Patient-reported outcomes for measuring the quality of life in advanced breast cancer treated with third-line and beyond chemotherapy-based regimens: A national cross-sectional study.
Authors: Xiuwen Guan, Xiaoyan Yan, Ying Wang, Xichun Hu, Xiaoying Sun, Zhanhong Chen, Xiaochen Zhang, Ying Dong, Wenyan Chen, Yanxia Shi, Jing Cheng, Zhihong Mei, Fei Ma
Journal: Journal of Clinical Oncology (2022)

1103 Background: Prolongation of survival and maintenance of quality of life (QoL) are the primary therapeutic goals in advanced breast cancer. Around 10% of adverse events (AEs) in the CTCAE are symptomatic AEs (e.g., nausea, sensory neuropathy), which can severely and directly affect the QoL of patients. However, seldom evidence mapped the QoL and symptomatic AEs utilizing patient-reported outcomes (PROs) in heavily pretreated breast cancer patients. This study aimed to investigate the PROs for measuring the QoL and symptomatic AEs of advanced breast cancer treated with third-line and beyond chemotherapy-based regimens in China. Methods: This national survey enrolled patients with advanced breast cancer receiving third-line and beyond chemotherapy-based regimens in 59 centers all over China from March to April in 2021. Each patient filled out a questionnaire containing demographic information, medical history, EORTC-QLQ-C30, and symptomatic AEs. The symptomatic AEs included fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, alopecia, fever, and limb numbness. The range method was used for the linear conversion of the PRO scores, which were converted into standardized scores of 0 to 100. Results: This study enrolled 1015 patients with the median age of 52 years. The QoL of all patients were poor, with the global health status score of 52.4±17.7 (Table). All the symptomatic AE scores were low among the patients. However, no significant differences were observed in global health status and symptomatic AEs between mono-chemotherapy and multi-agent chemotherapy (All P&gt;0.05). Conclusions: The QoL of advanced breast cancer patients treated with third-line and beyond chemotherapy were poor, especially in symptomatic AEs. In addition, the EOTRC-QLQ-C30 scale appears to underestimate the differences in symptomatic AEs between mono-chemotherapy and multi-agent chemotherapy, probably due to a lack of sensitivity of the scale, which fails to match the actual clinical observations of the PROs and QoL. Therefore, new scales need to be developed for the evaluation of symptomatic AEs and QoL in advanced breast cancer. [Table: see text]
NGS analysis of germline mutation profile of patients with hepatocellular carcinoma in China.
Authors: Xiaobing Wu, Didi Guo, Tiantian Han, Yaping Zhao, Juan Ma, Guanghua Lu, Fanfeng Bu, Siqi Chen, Wanglong Deng, Ran Ding
Journal: Journal of Clinical Oncology (2022)

10585 Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide with very poor prognosis. Many studies have focused on oncogene characteristics, however, the germline landscape of Chinese HCC patients has not been fully clarified. The purpose of this study is to assess the inherited genetic factors regarding germline mutations in Chinese HCC patients. Methods: Genetic mutations were reviewed in 1670 Chinese HCC patients who underwent hybridization capture based next-generation sequencing (NGS). The pathogenicity of germline mutations was categorized based on American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Of 1670 patients with HCC, 110 (6.7%) patients were identified to carry 111 pathogenic variants(P) or likely pathogenic variants(LP) in 112-cancer predisposition gene panel, and there was no age difference between P/LP group and non-P/LP group (average age: 57 vs 56, p = 0.64). The most frequently germline mutated genes were BRCA1/2 (11.7%), followed by ATM(4.5%), BLM(4.5%), ERCC2(4.5%), ERCC3(4.5%) and BRIP1(3.6%), ERCC4(3.6%), FANCD2(3.6%), MUTYH(3.6%), RAD50(3.6%). Of all the 111 germline mutations, 47% (n = 52) lay in the Homologous Recombination Repair (HRR) pathways. Both in P/LP group and non-P/LP group, the most frequently somatic mutated genes were TP53, TERT and MUC16. 7/110(6.4%)of patients in P/LP group were high TMB(≥10 mutations/megabase) and 131/1560(8.5%) in non-P/LP group. There was no statistical difference in TMB between P/LP and non-P/LP group. Conclusions: Taken together, we have presented the spectrum of pathogenic germline mutations in Chinese HCC patients. P/LP germline variants in cancer predisposition genes were detected in 6.7% of those patients, and predisposition genes associated with HCC risk needs further investigation. Inherited genetics should not be overlooked in HCC as there are important implications for precision treatment, future risk of cancers, and familial cancer risk.
Correspondence on 'Novel imaging biomarkers predict outcomes in stage III unresectable non-small cell lung cancer treated with chemoradiation and durvalumab' by Jazieh <i>et al</i>
Authors: Jieling Zheng, Bin Zhang
Journal: Journal for ImmunoTherapy of Cancer (2022)

Dear Editor, We read with great interest the study by Jazieh et al ,[1][1] recently published in the Journal for ImmunoTherapy of Cancer . Consolidation immunotherapy after chemoradiation has already become the standard of care for locally advanced, unresectable non-small cell lung cancer (NSCLC)
Efficacy and safety of 448 kHz capacitive-resistive radiofrequency electrotherapy for organic erectile dysfunction: A pilot study
Authors: D. Korolev, L. Chuvalov, A. Shpikina, D. Fiev, I. Lumpov, Y. Gorobec, V. Kozlov, S. Shterengarts, M. Taratkin, D. Enikeev, L. Rapoport, M. Enikeev
Journal: European Urology (2022)
Facility type and late-stage Thyroid Hürthle Cell Adenocarcinoma: A NCDB Review.
Authors: Darby Keirns, Peter T. Silberstein, Vincent Eaton
Journal: Journal of Clinical Oncology (2022)

e18074 Background: Hürthle cell adenocarcinoma, or oxyphilic adenocarcinoma, is a rare and invasive cancer accounting for 3-4% of all thyroid malignancies. Surgical removal is the most common treatment. Survival differences based on treatment facility have been identified in other cancers, but this has not yet been studied in Hürthle cell adenocarcinoma. This study utilizes the National Cancer Database (NCDB) to investigate facility survival differences. Methods: Using the NCDB, 2,900 patients with stage III or IV oxyphilic adenocarcinoma of the thyroid were identified with ICD-O-3 histology code 8290/3 and primary site C739 between years 2004 and 2016. Facility types included community cancer, comprehensive community cancer, academic/research, and integrated network cancer programs. Between-facility type survival differences were estimated by the Kaplan-Meier method and associated log-rank tests. Descriptive statistics of race, sex, stage, facility location, urban/rural 2013, primary payer, median income quartile, and Charlson-Deyo score were used. All analysis was conducted using SPSS statistical software version 27. Results: Survival data was available for 2,017 stage III patients and 644 stage IV patients. In stage III, survival was lower in community programs when compared to academic/research (p = .011) and integrated network programs (p = .017). In stage IV, survival was also lower in community programs when compared to academic/research (p = .007) and integrated network programs (p = .011). No significant difference was seen within other comparisons. In both stages, the highest percentage of patients were white, had a Charlson-Deyo score of 0, and were treated in an urban metro area. Sex and facility location were variable among all stages and facilities. In stage III, private insurance was most common overall and for academic/research programs, but Medicare was the majority for other facility types. In stage IV, Medicare was most common overall and for each facility. The median income quartile was &gt; $63,000 across all facility types for stage III and overall for stage IV, although stage IV treated in community and integrated network programs were most commonly between $48,000-$62,999. Conclusions: Patients with late-stage Hürthle cell adenocarcinoma have worse survival when treated in a community program than other facility types. Most demographics were consistent across stage and facility type, except for sex, primary insurance, median income, and facility location. This data contributes to a developing understanding of differences in cancer survival.[Table: see text]
HGG-23. The presence of<i>ROS1</i> fusions are not limited only to infantile hemispheric glioma.
Authors: Joanna Trubicka, Maciej Ciołkowski, Marta Perek-Polnik, Bożenna Dembowska-Bagińska
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Diffuse pediatric-type high-grade gliomas are diffuse gliomas with histological features of malignancy, typically occurring in children, and infants. For these tumors, precise classification, identification of prognostic and predictive factors requires molecular analysis. The ROS proto-oncogene 1 (ROS1) gene encodes a receptor tyrosine kinase that is involved in chromosomal rearrangements in numerous malignancies, and may be an attractive therapeutic target, since specific inhibitors have been approved for several neoplasms. Molecular evaluation including detection of ROS1 fusions in pediatric gliomas are not included in standard diagnostic tests so far, therefore data on its significance is still limited. We present two cases of pediatric ROS1 fusion-positive brain tumors. METHODS AND RESULTS: The patient no.1 was 1 year old boy with disseminated brain lesions. Histopathological examination displayed the presence of a neoplasm, which was composed of round and spindle-shaped cells with palisading necrosis, mitotic activity, and microvascular proliferation. The patient no.2 is 9 years old girl with tumor located in left frontal lobe. Microscopically, the neoplasm revealed the presence of oligodenroglial-like component with microvascular proliferation, and high mitotic activity. Targeted gene sequencing panel - Ampliseq Childhood Cancer Panel for Illumina was used to detect diagnostic and targetable gene fusions. In both of patients ROS1:GOPC gene fusions were detect. Identified fusions allowed to established diagnosis - infant-type hemispheric glioma with ROS1 fusion (patient no 1) and - diffuse pediatric-type high grade glioma with ROS1 fusion (patient no 2). CONCLUSIONS: Our results indicate, that the presence of ROS1 fusions are not limited to the infant-type hemispheric gliomas only and may play a role in other glioma entities. It may be worth to include this biomarker in the diagnostic panel of pediatric brain tumors to establish a more precise diagnosis and a potential therapeutic target. Funded by National Science Centre, Poland (2016/23/B/NZ2/03064).
Safety and effectiveness of avelumab in patients with curatively unresectable merkel cell carcinoma (MCC) in a real-world setting: A post-marketing surveillance in Japan.
Authors: Hisashi Uhara, Yoshio Kiyohara, Masashi Sato, Shehla Endo, Bingbing Song, Yoshinori Sato, Yutaro Tanaka, Anzu Kambe, Naoya Yamazaki
Journal: Journal of Clinical Oncology (2022)

e21528 Background: Avelumab is an anti–PD-L1 monoclonal antibody that was approved in Japan for the treatment of patients with curatively unresectable MCC in Sept 2017. Because the number of Japanese patients with MCC participating in the global Phase II JAVELIN Merkel 200 study was limited (3 patients), Japan was mandated to conduct an all-case surveillance as a post-marketing surveillance (PMS) study. In the all-case surveillance, safety and efficacy information is accumulated with respect to a defined period of time or a defined number of post-approval prescription cases and is provided as real-world data. This report summarizes the results of the final analysis of this MCC PMS. Methods: This PMS is a multicenter, non-comparative, prospective, observational study. Since Nov 2017 (following approval in Japan), all patients with MCC who received at least one dose of avelumab in Japan were enrolled, and case report forms (CRF) were collected for all patients who started treatment through Oct 2019. Results: As of Sept 22, 2021, 152 patients from 86 sites were enrolled, and CRFs were collected from 77 patients. Of the 75 patients (53 sites) who met the analysis adequacy criteria, 48% were female, and the median age at the start of avelumab treatment was 77.0 years (42-95 years). Of the treatment lines in which avelumab was administered, 93.3% (70/75) were prescribed as first-line therapy. The incidence of adverse reactions was 61.3% (46/75), and 9.3% (7/75) discontinued treatment due to adverse reactions. Grade 3 and 4 adverse reactions occurred in 12.0% (9/75) and 4.0% (3/75), respectively; no grade 5 adverse reactions were reported. Infusion reactions were reported in 28.0% (21/75). The objective response rate (proportion of patients whose best response was assessed by the investigator as a complete or partial response) up to 1 year after the start of avelumab treatment was 45.3% (95% CI: 33.8, 57.3). The 1-year overall survival rate was 59.6% (95% CI: 47.0, 70.1). Conclusions: This study report is the first real-world evidence collected and analyzed from actual clinical use of avelumab in patients with curatively unresectable MCC in the East Asia region. Despite the different baseline patient characteristics, avelumab therapy in clinical practice had a manageable safety profile with no new safety concerns and has shown similar efficacy to that observed in the JAVELIN Merkel 200 trial.
Durability of Protection Against Symptomatic COVID-19 Among Participants of the mRNA-1273 SARS-CoV-2 Vaccine Trial
Authors: Dan-Yu Lin, Lindsey R. Baden, Hana M. El Sahly, Brandon Essink, Kathleen M. Neuzil, Lawrence Corey, Jacqueline Miller, Moni B Neradilek, Holly Janes, Weiping Deng, Honghong Zhou
Journal: JAMA Network Open (2022)